This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The purpose of the current study is to determine if hOKT3 (Ala-Ala) will be effective in the long-term treatment of psoriatic arthritis.Previously, hOKT3?1 (Ala-Ala) has been administered as a 10 to 14 day single course. In the Phase I /II trial, we observed apparent efficacy from a single course of hOKT3?1 (Ala-Ala) for PsA, however responses in most participants were transient. Furthermore, only mild skin disease was transiently responsive to a single course of hOKT3?1 (Ala-Ala). Significant long-term benefit for both the arthritis and skin disease may require repeated cycles of hOKT3?1 (Ala Ala). This hypothesis is based on clinical experience and the postulated mechanisms of non-Fc receptor binding antibodies. Only activated lymphocytes that have developed a Th1 phenotype should be sensitive to the anergizing potential of the antibody. Furthermore, polarization of peripheral T cell populations requires repeated rounds of stimulation.It is postulated that a five-day infusion cycle will be as efficacious as the longer cycle used in the Phase I /II study. This is based on the observation that substantial T cell population depletion occurs rapidly following 4-mg doses of hOKT3?1 (Ala-Ala). In our initial study, administration of an initial maximum dose of 4 mg was associated with significant side-effects. However, a rapid escalation of the dose of hOKT3?1 (Ala-Ala) from 1 mg on the first day to 2 mg on the second and 4 mg on the third was well tolerated. Therefore, the proposed five-day cycle of daily treatments described below should safe as well as efficacious. Furthermore, five-day cycles of drug will facilitate the use of hOKT3?1 (Ala-Ala) in an outpatient setting:The study drug will be administered as a daily infusion in 5-day cycles. Dosing includes an escalating dose phase over the first 3 days of each 5-day cycle. On the first day of treatment, the participant will receive 1 mg. On Day 2 the participant will receive 2 mg. From Days 3 to 5 the participant will receive a daily dose of 4 mg. Subsequent cycles are administered monthly (at least 28 days post-Day 5 infusion of the prior cycle) for a total of 4 cycles.
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